C A S E R E P O R T

Role of imaging in herpes and Japanese encephalitis –

Two cases and review of literature

Shibani Mehra*, UC Garga**

Abstract

Inflammatory involvement of brain parenchyma by viral infections is common in both developing and developed countries. Viral

infection of cerebral parenchyma is characterised by inflammation as well as neuronal degeneration. Japanese encephalitis is the

commonest endemic human encephalitis in the world, while herpes encephalitis is the most common sporadic encephalitis.

MR imaging has facilitated the early and accurate diagnosis of these fatal infections and thereby played a significant role in reducing

morbidity by instituting adequate therapeutic protocols at the adequate stage of illness.

Key words: JE, CT, MRI, T1W, T2W, DWI, ADC, GRE, FLAIR.

Introduction

Type I herpes simplex virus is the cause of 95% of fatalencephalitis in adults1. However, in the paediatric andneonatal population, herpes simplex virus type 2 is theaetiological culprit in 80 - 90% patients2. The diseaseresults from reactivation of the latent virus from apreviously infected ganglion and progresses to itsflagrant form. Herpes encephalitis has a range of clinicalpresentations from aseptic meningitis and fever to arapidly progressive form involving loss ofconsciousness. Early intervention with acyclovirimproves the outcome.

JE is the commonest endemic encephalitis in South-EastAsia including India where the first case was detected inVellore. JE virus is a single-stranded RNA flavivirus whichbelongs to the JE sero-complex composed of 10flaviviruses. The virus is transmitted to humans via infectedculex mosquitoes and propagates at the site of bite andin the regional lymph nodes. The virus is neurotropic andcan invade the CNS. Viraemia develops and involves theheart, lungs, liver, and RE system as a subclinical disease3.There is a high incidence of Japanese encephalitis in thepaediatric population with high mortality. Although themanagement is supportive therapy, proper diagnosisassists in reducing morbidity.

We are presenting the imaging appearances in a case eachof herpes encephalitis and Japanese encephalitis anddiscussing the importance of MR imaging in making anaccurate and early clinical diagnosis by detecting thetypical sites of parenchymal involvement by each of thesefatal viruses. We highlight the ability of MRI indifferentiating the two infections from each other.

Case report 1

A 54-year-old male presented with history of high gradefever, and headache of three days duration, followed byloss of consciousness with onset of confusion and deliriumon the fourth day progressing to coma. Increased proteinand leukocyte count were shown on routine CSF analysis.CSF polymerase chain reaction was performed on the fifthday and viral antibodies were detected.

CT scanning with intravenous contrast performed onPhilips multidetector spiral scanner showed diffusehypodense lesions in bilateral frontal and anterior medialtemporal cortices with no uptake of intravenous contrast.MR imaging in axial, sagittal, and coronal planes was

* Associate Professor, ** Professor, Department of Radiology,

PGIMER, Dr. Ram Manohar Lohia Hospital, Baba Kharak Singh Marg, New Delhi - 110 001.

Fig. 1a: T1-weighted axial MR image shows hypointense signal intensity in

symmetrically distributed lesions in bilateral basifrontal, frontal, and left

antero-medial temporal cortex.

JIACM 2012; 13(4): 338-43

subsequently performed on a 1.5 Tesla SiemensSomatom Balance Scanner on the fourth day. T1Wimages were obtained with TR of 600 and TE of 15; whileT2W images were obtained with TR 4,000 and TE 150.The MR images demonstrated involvement of bilateralbasi-frontal, frontal, and left antero-medial temporalcortex with the lesions appearing hypointense on T1Wimages and hyperintense on T2W and FLAIR images (Fig.1a, b, c). Sulcal effacement and cortical oedema were alsoappreciated. Tiny foci of blooming were detected in thelesions on gradient echo images indicating presence ofpetechial haemorrhage (Fig. 2a, b). DW1 imagesdemonstrated diffusion restriction in the lesion in the

form of bright signal intensity. Post-gadolinium T1images did not reveal any contrast uptake norenhancement in the affected fronto-temporal cortex.The characteristic involvement of bilateral inferior frontal,frontal, and left medial temporal cortex alongwithidentification of petechial haemorrhage and restricteddiffusion in the lesions enabled the diagnosis of herpesencephalitis by imaging. The patient, however,deteriorated fast and could not be saved inspite ofacyclovir administration at this point.

Fig. 1b, c: Sagittal T2 -weighted and axial FLAIR MR images demonstrate

hyperintense signal intensity in the frontal, basi-frontal and temporal

lesions with associated sulcal effacement.

Fig. 2a: Gradient echo axial MR images showing petechial haemorrhage

in bilateral basi-frontal cortex and subcortical white matter seen as tiny

black foci described as ‘blooming’.

Fig. 2b, c: Diffusion-weighted MR image shows restricted diffusion in

bilateral basi-frontal and frontal cortex, seen as bright signal intensity.

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Case report 2

An 8-year-old boy was admitted in the paediatricemergency with high-grade fever and bodyache of fourdays duration with onset of irritability and alteredsensorium on the fourth day. The routine CSF analysisrevealed pleocytosis and lymphocyte predominance whilespecific serology examination showed evidence of viralantibodies which were thought to be due to virus infection.

Contrast-enhanced CT of the brain performed on PhilipsBrilliance 40 slice spiral scanner showed hypodense, non-enhancing, bilateral thalamic and pontine lesions (Fig. 3a,b). MR imaging was performed on Siemens 1.5 Tesla

scanner using polarised head coil to further evaluate thethalamic lesions. T1, T2-weighted, FLAIR T2, echoplanardiffusion-weighted and gradient echo images were takenin all the three orthogonal planes.

The images demonstrated bilateral symmetricallydistributed T1 hyperintense lesions in the thalami andpons with similar, though asymmetric, involvement of rightmid-brain (Fig 4a). On T2-weighted and FLAIR images too,these lesions appeared hyperintense (Fig. 4b, c). Bloomingwas seen at the periphery of the thalamic lesions as wellas the pontine lesions on GRE images (Fig. 5); while DW1images showed diffusion restriction in the lesions. Therewas no contrast uptake by lesions on gadoliniumadministration. A diagnosis of Japanese encephalitis wasmade on visualisation of haemorrhagic lesions involvingthe deep grey matter as well as the brainstem. Bilateralsymmetric lesions in the thalamus raised the suspicion ofJapanese encephalitis and this was confirmed by ELISAdetection of the specific antibodies.

Discussion

Both herpes and Japanese encephalitis are haemorrhagicencephalitis with a fulminant clinical course. Earlydiagnosis and institution of proper therapy is importantin order to reduce both morbidity and mortality. Imaginghas the main role in the early and accurate diagnosis ofthese entities. MR imaging detects the characteristic sitesof parenchymal involvement by these fatal viruses,thereby differentiating these two from each other and alsofrom other encephalitis, as no other encephalitis isassociated with haemorrhage.

The herpes virus preferentially involves the temporal lobe

Fig. 3a, b: Axial CT images of the brain demonstrate bilateral thalamic

hypodense lesions in a; and hypodense pontine lesions in b.

Fig. 4a: Sagittal TI-weighted MR image shows hyperintense signal intensity

in the thalamic, mid-brain, and pontine lesions.

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and orbital surfaces of the frontal lobe. The infection mayextend to the insular cortex, the posterior occipital cortex,and the cerebral convexities. Bilateral involvement isfrequent. Pathologically, herpetic involvement of cerebralparenchyma is a fulminant and necrotisingmeningoencephalitis with severe tissue necrosis andoedema; and petechial haemorrhages are a part of the

haemorrhagic necrosis4.

Imaging plays a major role in reducing mortality from thisfatal infection by demonstrating the classic involvementof bilateral basi-frontal and medial temporal lobes inherpes encephalitis. Such involvement is consistent withintracranial spread along the small meningeal branchesof the cranial nerve5. Pontine lesions too may occur dueto retrograde transmission of infection along the cisternalportion of the trigeminal nerve.

In the CT images, the lesions appear hypodense, anddiffuse involvement of bilateral temporal lobes andorbital surfaces of frontal lobes can be detected. Onintravenous contrast administration, patchy gyralenhancement may be seen late in the disease process,though usually no enhancement is seen5. The greaterthe number of lesions detected on CT scanning, thelower is the patient’s score on the Glasgow Coma Scale.However CT scanning may not reveal any abnormalityuntil 3 - 5 days after the disease by which time the patientmay become comatose. Reports exist of patients withnormal CT and abnormal MRI.

MR imaging is definitely superior to CT imaging as thespecific anatomic regions involved by the virus are clearlydelineated. The bilateral involvement typical of herpeticencephalitis is better appreciated on MR, and the petechialhaemorrhages which are not detected on CT images arevery well demonstrated. MR imaging in herpesencephalitis shows T1 hypointense, T2 hyperintense

Fig. 4b and c: FLAIR sagittal and FLAIR coronal images demonstrate

hyperintense signal in bilateral thalami, basal ganglia, and in the brainstem.

Fig. 5: Haemorrhage visualised at the periphery of the pontine lesions as

blooming in this axial gradient echo T2 image.

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lesions in the characteristic distribution involving thecortex of medial temporal as well as the inferior frontallobes6. Bilateral involvement without respect forhippocampal borders is seen. GRE images demonstratethe petechial haemorrhage characteristic of herpesencephalitis in the form of dark foci described as foci of‘blooming’. The cytotoxic oedema and restricted waterdiffusion associated with the parenchymal inflammationpresents in the DW image as bright signal intensity withlow signal intensity in the ADC images7. MR spectroscopydemonstrates a reduction of NAA to choline ratio,reflecting neuronal injury. NAA recovery parallels clinicalimprovement.

In neonates and infants, MR appearance of herpeticencephalitis is different with periventricular white matterinvolvement being encountered rather than the typicalfronto-temporal distribution seen in adults. Meningealenhancement is more commonly seen as is patchy gyralor parenchymal enhancement on Gadoliniumadministration8.

The initial presentation of Japanese encephalitis isnonspecific, the symptoms starting with a prodrome offever, headache, and vomiting leading to seizures. Motoror cranial nerve palsies and even acute flaccid paralysismay develop. A very distinctive clinical presentation of JEresulting from extrapyramidal involvement is aParkinsonism-like syndrome with tremors, and involuntarymovements and may be encountered9. The confirmationof clinical diagnosis is done by detecting rising JE virusantibody titres in the sera or in the CSF, using ELISA; andthe results usually take one to three weeks. Therefore,radiologic imaging plays a major role in the early diagnosisof JE.

The CNS involvement in JE is in the form of bilateral, oftenhaemorrhagic, predominantly thalamic, putaminal,pontine, as well as cerebellar lesions. The mid-brain,hippocampus, and cerebral cortex too may be involved.Radiologic imaging is crucial in early diagnosis of JE andits differentiation from HS encephalits. The deep greymatter involvement detected on MR is characteristic anddiagnostic of JE, though white matter involvement has alsobeen reported.

The most characteristic MR finding is T2 and FLAIRhyperintense lesions in bilateral thalami10. On T1W images,the lesions appear hypointense while lesions withhaemorrhagic transformation demonstratecorresponding T1 hyperintensity, with no enhancementof the lesions on Gadolinium administration. Dark signalareas described as “blooming” are identified on GRE MRimages. Diffusion weighted MR sequences have the

advantage of detecting more number of lesions, theirdetection earlier than any other means, as well asidentifying the stage of infection. The ischaemia andcytotoxic oedema due to perivascular cuffing in acute JEleads to restricted diffusion and low ADC values ondiffusion MR imaging. In the subacute stage, theproportion of diffusion restriction decreases in DW imageand ADC starts rising while necrosis and demyelinationin the chronic stage results in hypointensity on DW1 andhigh ADC values11.

Differential diagnosis

MR imaging differentiates both HSE and JE by locatingthe typical anatomic sites of involvement of each virus.The deep gray matter involvement is an importantdistinguishing feature of Japanese encephalitis fromherpetic encephalitis in which cortical involvement occurspredominantly. MR imaging is extremely sensitive indetecting both thalamic and extrathalamic lesions.Moreover, it identifies the petechial haemorrhageassociated with HSE and the overt haemorrhage seen inmost lesions of JE. DW images demonstrate the cytotoxicoedema and restricted diffusion.

Bilateral thalamic haemorrhagic lesions identified in JE arealso seen in thalamic infarcts caused due to cerebral deepvein thrombosis or due to stenoses, occlusion, orthrombosis of the basilar artery.

On MR, T1 hyperintense bilaterally symmetric lesions arealso detected in some other disorders but the sites ofcerebral involvement and MR appearances differ:-

a. Degenerative diseases such as hepato-cerebraldegeneration demonstrate T1 hyperintense lesionsin globus pallidus, putamen, and rarely themesencephalon.

b. Wilson’s disease presents in childhood with acharacteristic clinical picture; the globus pallidus,putamen, caudate nucleus, thalamus, and mid-brainshow lesions with increased signal intensity on T1 aswell as T2 images.

c. Metabolic derangement of Wernicke’s encephalo-pathy, encountered due to alcohol abuse leads tothiamine deficiency and periacqueductal grey matter,mamillary body and mid-brain involvement with T1hyperintense lesions.

Post-viral autoimmune demyelination (ADEM) which is aninflammatory demyelination and therefore involves thewhite matter, may demonstrate haemorrhage and beconfused with HSE; but ADEM is preceded by a viral illnessand has a sub-acute onset.

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Conclusion

MR imaging with its multiplanar capability can identifythalamic, basal ganglia, pontine as well as posterior fossalesions with ease and is thereby superior to CT imaging.GRE images on MR are very useful in detecting thehaemorrhage, while diffusion MR detects the cytotoxicoedema . Each patient with neurologic symptoms of acuteonset must therefore undergo MR imaging for accuratediagnosis of these viral encephalitis. Imaging can allow earlydiagnosis and save mortality from these fatal encephalitis.

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